Atropisomeric α-methyl substituted analogues of 4-(dimethylamino)pyridine: synthesis and evaluation as acyl transfer catalysts

Abstract

The regioselectivity of α-metalation–methylation of N-BF₃ adducts of 4-(dimethylamino)pyridines as a function of β-substitution is examined in attempts to prepare configurationally stable atropisomeric derivatives (I and II) having an α-methyl substituent and a β-biaryl stereogenic axis. The activity of some of these derivatives as catalysts for acyl transfer is examined and the kinetic resolution of 1-(1-naphthyl)ethanol catalysed by α-methyl chiral DMAP (−)-24 is reported. A rationale for the reduced stereoselectivity of this catalyst relative to its non-α-substituted analogue (−)-1 is also proposed.